Autoantigen-specific CD4 T cells acquire an exhausted phenotype and persist in human antigen-specific autoimmune diseases.

Pro-inflammatory autoantigen-specific CD4 T helper (auto-Th) cells are central orchestrators of autoimmune diseases (AIDs). We aimed to characterize these cells in human AIDs with defined autoantigens by combining human leukocyte antigen (HLA)-tetramer-based and activation-based multidimensional ex vivo analyses. In aquaporin4-antibody-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD) patients, auto-Th cells expressed CD154, but proliferative capacity and pro-inflammatory cytokines were strongly reduced.

Neurofilament light (NfL) concentrations in patients with epilepsy with recurrent isolated seizures: Insights from a clinical cohort study.

Purpose: To detect possible neuronal damage due to recurrent isolated seizures in patients with epilepsy in a clinical routine setting.

Methods: We measured the serum concentrations of neurofilament light chain (sNfL) in 46 outpatients with an at least monthly occurrence (self-reported) of generalized tonic-clonic seizures in the six months prior to the study and in 49 patients who had been seizure free (self-reported) for at least one year. We assigned the patients with seizure activity into groups with moderate and high seizure frequency.

Cycle threshold of SARS-CoV-2 RT-PCR as a driver of retesting.

SARS-CoV-2 RT-PCR is a critical and, at times, limited resource. Frequent Retesting of patients may strain testing infrastructure unduly. Recommendations that include cycle threshold (Ct) cutoffs may incentivize early retesting when the Ct value is reported.

Aβ38 and Aβ43 do not differentiate between Alzheimer's disease and cerebral amyloid angiopathy.

Differential diagnosis between Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA) using cerebrospinal fluid (CSF) biomarkers is challenging. A recent study suggested that the addition of Aβ38 and Aβ43 to a standard AD biomarker panel (Aβ40, Aβ42, t-tau, p-tau) to improve the differential diagnosis. We tested this hypothesis in an independent German cohort of CAA and AD patients and controls using the same analytical techniques.

Anti-SEZ6L2 antibodies in paraneoplastic cerebellar syndrome: case report and review of the literature.

Seizure Related 6 Homolog Like 2 (SEZ6L2) protein has been shown to have implications in neuronal and especially motor function development. In oncology, overexpression of SEZ6L2 serves as a negative prognostic marker in several tumor entities. Recently, few cases of anti-SEZ6L2 antibody mediated cerebellar syndromes were reported.

Anti-flotillin-1/2 antibodies in a patient with neurogenic muscle atrophy and mild neuropsychological impairment.

Autoimmune-mediated neural inflammation can affect both the central and the peripheral nervous system. Recently, antibodies against the peripheral membrane protein flotillin have been described in patients with multiple sclerosis, limbic encephalitis and sensorimotor demyelinating polyneuropathy. Here, we report the case of a 75-year-old male patient presenting with slowly progressive muscle weakness, as well as mild cognitive impairment.

B-cell responses to vaccination with BNT162b2 and mRNA-1273 6 months after second dose.

Objectives: To examine the state of B-cell immunity 6 months after the second vaccination against SARS-CoV-2 in comparison to the state observed 2 weeks after vaccination.

Methods: Sera of 439 participants, whose immune responses to two doses of an mRNA-based vaccine (BNT162b2 or mRNA-1273) were previously characterized, was examined for anti-S1 IgG and IgA, anti-NCP IgG and neutralizing antibodies (nAb), and antinuclear antibodies (ANA).

Results: Levels of all examined markers decreased significantly from 2 weeks to 6 months after second vaccination (anti-S1 IgG: 3744 ± 2571.

Clinical, serological and genetic predictors of response to immunotherapy in anti-IgLON5 disease.

Anti-IgLON5 disease is a newly defined clinical entity characterized by a progressive course with high disability and mortality rate. While precise pathogenetic mechanisms remain unclear, features characteristic of both autoimmune and neurodegenerative diseases were reported. Data on immunotherapy are limited, and its efficacy remains controversial.

Kinetics of the Antibody Response to Boostering With Three Different Vaccines Against SARS-CoV-2.

Background: Heterologous vaccinations against SARS-CoV-2 with ChAdOx1 nCoV-19 and a second dose of an mRNA-based vaccine have been shown to be more immunogenic than homologous ChAdOx1 nCoV-19. In the current study, we examined the kinetics of the antibody response to the second dose of three different vaccination regimens (homologous ChAdOx1 nCoV-19 vs. ChAdOx1 nCoV-19 + BNT162b2 or mRNA-1273) against SARS-CoV-2 in a longitudinal manner; whether there are differences in latency or amplitude of the early response and which markers are most suitable to detect these responses.

The temporal course of T- and B-cell responses to vaccination with BNT162b2 and mRNA-1273.

Objectives: To investigate the response of the immune system (and its influencing factors) to vaccination with BNT162b2 or mRNA-1273.

Methods: 531 vaccinees, recruited from healthcare professionals, donated samples before, in between, and after the administration of the two doses of the vaccine. T- and B-cell responses were examined via interferon-γ (IFN-γ) release assay, and antibodies against different epitopes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (S1 and NCP) were detected via ELISA and surrogate neutralization assay.

Analysis of SARS-CoV-2 reverse transcription-quantitative polymerase chain reaction cycle threshold values vis-à-vis anti-SARS-CoV-2 antibodies from a high incidence region.

Objectives: To examine the relationship between antibody status and cycle threshold (Ct) values, the prognostic value of the latter for COVID-19 patients, and the inter-assay comparability of SARS-CoV-2 Ct values.

Methods: In 347 COVID-19 inpatients, SARS-CoV-2 Ct values (via reverse transcription-quantitative polymerase chain reaction) on admission were compared between 2 assays and correlated with the antibody response (in the course of the disease), the clinical course and the time since onset of symptoms.

Results: Ct values for 2 of 3 target genes showed significant differences between the 2 assays used (P=0.

Immunogenicity and safety of anti-SARS-CoV-2 mRNA vaccines in patients with chronic inflammatory conditions and immunosuppressive therapy in a monocentric cohort.

Introduction: In light of the SARS-CoV-2 pandemic, protecting vulnerable groups has become a high priority. Persons at risk of severe disease, for example, those receiving immunosuppressive therapies for chronic inflammatory cdiseases (CIDs), are prioritised for vaccination. However, data concerning generation of protective antibody titres in immunosuppressed patients are scarce.

Clinical correlates of anti-SARS-CoV-2 antibody profiles in Spanish COVID-19 patients from a high incidence region.

Laboratory testing for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) consists of two pillars: the detection of viral RNA via rt-PCR as the diagnostic gold standard in acute cases, and the detection of antibodies against SARS-CoV-2. However, concerning the latter, questions remain about their diagnostic and prognostic value and it is not clear whether all patients develop detectable antibodies. We examined sera from 347 Spanish COVID-19 patients, collected during the peak of the epidemic outbreak in Spain, for the presence of IgA and IgG antibodies against SARS-CoV-2 and evaluated possible associations with age, sex and disease severity (as measured by duration of hospitalization, kind of respiratory support, treatment in ICU and death).

Longitudinal Multi-omics Analyses Identify Responses of Megakaryocytes, Erythroid Cells, and Plasmablasts as Hallmarks of Severe COVID-19.

Temporal resolution of cellular features associated with a severe COVID-19 disease trajectory is needed for understanding skewed immune responses and defining predictors of outcome. Here, we performed a longitudinal multi-omics study using a two-center cohort of 14 patients. We analyzed the bulk transcriptome, bulk DNA methylome, and single-cell transcriptome (>358,000 cells, including BCR profiles) of peripheral blood samples harvested from up to 5 time points.

Low-Avidity CD4 T Cell Responses to SARS-CoV-2 in Unexposed Individuals and Humans with Severe COVID-19.

CD4 T cells reactive against SARS-CoV-2 can be found in unexposed individuals, and these are suggested to arise in response to common cold coronavirus (CCCoV) infection. Here, we utilized SARS-CoV-2-reactive CD4 T cell enrichment to examine the antigen avidity and clonality of these cells, as well as the relative contribution of CCCoV cross-reactivity. SARS-CoV-2-reactive CD4 memory T cells were present in virtually all unexposed individuals examined, displaying low functional avidity and multiple, highly variable cross-reactivities that were not restricted to CCCoVs.